Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched...

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Veröffentlicht in:Biology of blood and marrow transplantation 2016-08, Vol.22 (8), p.1376-1382
Hauptverfasser: Wang, Yu-Tong, Kong, Yuan, Song, Yang, Han, Wei, Zhang, Yuan-Yuan, Zhang, Xiao-Hui, Chang, Ying-Jun, Jiang, Zheng-Fan, Huang, Xiao-Jun
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container_end_page 1382
container_issue 8
container_start_page 1376
container_title Biology of blood and marrow transplantation
container_volume 22
creator Wang, Yu-Tong
Kong, Yuan
Song, Yang
Han, Wei
Zhang, Yuan-Yuan
Zhang, Xiao-Hui
Chang, Ying-Jun
Jiang, Zheng-Fan
Huang, Xiao-Jun
description Abstract Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.
doi_str_mv 10.1016/j.bbmt.2016.04.016
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The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT.</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2016.04.016</identifier><identifier>PMID: 27131864</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Allogeneic hematopoietic stem cell transplantation ; Bone Marrow - immunology ; Bone marrow immune microenvironment ; Case-Control Studies ; CD4-CD8 Ratio ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Graft Survival - immunology ; Hematology, Oncology and Palliative Medicine ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-gamma - analysis ; Interleukin-4 - analysis ; Male ; Middle Aged ; Poor graft function ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes, Cytotoxic ; Th1 Cells ; Th2 Cells ; Transplantation, Homologous ; Transplants - cytology ; Transplants - immunology ; Type 1 and type 2 immune responses ; Young Adult</subject><ispartof>Biology of blood and marrow transplantation, 2016-08, Vol.22 (8), p.1376-1382</ispartof><rights>American Society for Blood and Marrow Transplantation</rights><rights>2016 American Society for Blood and Marrow Transplantation</rights><rights>Copyright © 2016 American Society for Blood and Marrow Transplantation. 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The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. 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The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4+ and CD8+ T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8+ T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. 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subjects Adolescent
Adult
Allogeneic hematopoietic stem cell transplantation
Bone Marrow - immunology
Bone marrow immune microenvironment
Case-Control Studies
CD4-CD8 Ratio
Child
Child, Preschool
Female
Flow Cytometry
Graft Survival - immunology
Hematology, Oncology and Palliative Medicine
Hematopoietic Stem Cell Transplantation
Humans
Interferon-gamma - analysis
Interleukin-4 - analysis
Male
Middle Aged
Poor graft function
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Cytotoxic
Th1 Cells
Th2 Cells
Transplantation, Homologous
Transplants - cytology
Transplants - immunology
Type 1 and type 2 immune responses
Young Adult
title Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation
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